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07-SEPTEMBER-2008 03:17:44 - Cytotoxic T cell Redirected from Cytotoxic T cells Antigen presentation stimulates T cells to become either cytotoxic CD8+ cells or helper CD4+ cells. Antigen presentation stimulates T cells to become either cytotoxic CD8+ cells or helper CD4+ cells. A cytotoxic T cell also known as TC, CTL, T-Killer cell, CD8+ T-cells or killer T cell belongs to a sub-group of T lymphocytes a type of white blood cell which are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses or other pathogens, or are otherwise damaged or dysfunctional. Most cytotoxic T cells express T-cell receptors TcRs that can recognize a specific antigenic peptide bound to Class I MHC molecules, present on all nucleated cells, and a glycoprotein called CD8, which is attracted to non-variable portions of the Class I MHC molecule. The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound closely together during antigen-specific activation. CD8+ T cells are recognized as TC cells once they become activated and are generally classified as having a pre-defined cytotoxic role within the immune system. Contents 1 Cytotoxic T cell development 2 Cytotoxic T cell activation 3 Cytotoxic T cell effector functions 4 Cytotoxic T cell role in disease pathogenesis 5 References Cytotoxic T cell development Development of single positive T cells in the thymus Development of single positive T cells in the thymus Hematopoetic stem cells in the bone marrow migrate into the thymus, where they undergo VDJ recombination of their beta-chain TcR DNA to form a developmental form of the TcR protein, known as pre-TcR. If that rearrangement is successful, the cells then rearrange their alpha-chain TcR DNA to create a functional alpha-beta TcR complex. This highly-variable genetic rearrangement product in the TcR genes helps create millions of different T cells with different TcRs, helping the body's immune system respond to virtually any protein of an invader. The vast majority of T cells express alpha-beta TcRs αβ T cells, but some T cells in epithelial tissues like the gut express gamma-delta TcRs γδ T cells, which recognize non-protein antigens. T cells with functionally stable TcRs express both the CD4 and CD8 co-receptors and are therefore termed double-positive DP T cells CD4+CD8+. The double-positive T cells are exposed to a wide variety of self-antigens in the thymus and undergo two selection criteria : 1 positive selection, in which those double-positive T cells that bind too weakly to MHC-presented self antigens undergo apoptosis because of their inability to recognize MHC-protein complexes. 2 negative selection, in which those double-positive T cells that bind too strongly to MHC-presented self antigens undergo apoptosis because their propensity to become autoreactive could lead to autoimmunity. Only those T cells that bind to the MHC-self-antigen complexes weakly are positively selected. Those cells that survive positive and negative selection differentiate into single-positive T cells either CD4+ or CD8+ dependent on whether their TcR recognizes an MHC class I presented antigen CD8 or an MHC class II presented antigen CD4. It is the CD8+ T-cells that will mature and go on to become cytotoxic T cells following their activation with a class I restricted antigen. Cytotoxic T cell activation With an exception of some cell types such as non-nucleated cells including erythrocytes, Class I MHC is expressed by all host cells. When these cells are infected with a virus or another intracellular pathogen, the cells degrade foreign proteins via antigen processing. These result in peptide fragments, some of which are presented by MHC Class I to the T cell antigen receptor TcR on CD8+ T cells. The activation of cytotoxic T cells is dependent on several simultaneous interactions between molecules expressed on the surface of the T cell and molecules on the surface of the antigen presenting cell APC. For instance, consider the two signal model for TC cell activation. Signal T cell APC Description first signal TcR peptide-bound MHC class I molecule There is a second interaction between the CD8 coreceptor and the class I MHC molecule to stablize this signal. second signal CD28 molecule on the T cell either CD80 or CD86 also called B7-1 and B7-2 CD80 and CD86 are known as costimulators for T cell activation. This second signal can be assisted or replaced by stimulating the TC cell with cytokines released from helper T cells. Once activated, the TC cell undergoes clonal expansion with the help of a cytokine called Interleukin-2 IL-2 that is a growth and differentiation factor for T cells. This increases the number of cells specific for the target antigen that can then travel throughout the body in search of antigen-positive somatic cells. Cytotoxic T cell effector functions When exposed to infected/dysfunctional somatic cells, TC cells release the cytotoxins perforin and granulysin. Perforin form pores in the target cell's plasma membrane allowing granzymes, a serine protease, to enter the target cell which then activate a series of enzymes, the caspase cascade, that eventually lead to apoptosis cell death. A second way to induce apoptosis is via cell-surface interactions between the TC and the infected cell. When a TC is activated it starts to express the surface protein FAS ligand FasL, which can bind to Fas molecules expressed on the target cell. However, this Fas-Fas ligand interaction is thought to be more important to the disposal of unwanted T lymphocytes during their development or to the lytic activity of certain TH cells than it is to the cytolytic activity of TC effector cells. Cytotoxic T cell role in disease pathogenesis Hepatitis B virus HBV infection During HBV infection cytotoxic T cells play an important pathogenetic role. They contribute to nearly all of the liver injury associated with HBV infection and, by killing infected cells and by producing antiviral cytokines capable of purging HBV from viable hepatocytes, cytotoxic T cells also eliminate the virus.1 Recently platelets have been shown to facilitate the accumulation of virus-specific cytotoxic T cells into the infected liver.2 References ^ Iannacone M. et al 2006. Pathogenetic and antiviral immune responses against hepatitis B virus. Future Virology 1 2: 189-196. doi:10.2217/17460794.1.2.189 Future Virology. ^ Iannacone M. et al 2005. Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat Med 11: 1167-1169. v d e Blood General Plasma - Hematopoietic stem cells Lymphoid - WBC T cells: Cytotoxic CD8+, Helper CD4+/Regulatory, γδ, Natural Killer T cell B cells: Plasma, Memory Natural killer cells Lymphokine-activated killer cell Null cell Myeloid - WBC Monocytes/Macrophages Histiocytes, Kupffer cells, Langhans giant cells, Microglia, Osteoclasts, Epithelioid cells Granulocytes Neutrophil, Eosinophil, Basophil - Mast cell precursors Dendritic cells Langerhans cells, Follicular dendritic cells Megakaryoblast - Megakaryocyte - Platelets Myeloid - RBC Reticulocyte - Normoblast v d e Immune system / Immunology Systems Adaptive immune system vs. Innate immune system · Humoral immune system vs. Cellular immune system · Complement system Anaphylatoxins · Intrinsic immune system Antibodies and antigens Antibody Monoclonal antibodies, Polyclonal antibodies, Autoantibody · Allotype · Isotype · Idiotype · Antigen Superantigen · Polyclonal B cell response Immune cells/White blood cells Lymphoid: T cell · B cell · NK cell Myeloid: Mast cell · Basophil · Eosinophil · Macrophage Phagocytes: Neutrophil · Macrophage/Reticuloendothelial system Professional APCs: Dendritic cell · Macrophage · B cell Immunity vs. tolerance Immunity · Autoimmunity · Allergy · Tolerance Central · Immunodeficiency Immunogenetics Somatic hypermutation · VDJ recombination · Immunoglobulin class switching · MHC/HLA Substances Cytokines · Opsonin · Cytolysin Other Inflammation · Epitope Linear epitope and Conformational epitope · Hapten · Cross-reactivity · Diagnostic immunology · Immune complex Retrieved from http://en..org/wiki/Cytotoxic_T_cell Categories: T cells | Human cells Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Česky Deutsch Français עברית Nederlands 日本語 Polski Português Svenska This page was last modified on 1 July 2008, at 08:03
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